Development and validation of a severity scoring system for Zellweger spectrum disorders

• Published in: Clinical genetics Vol. 93; no. 3; pp. 613 - 621
• Main Authors: Klouwer, F.C.C., Meester‐Delver, A., Vaz, F.M., Waterham, H.R., Hennekam, R.C.M., Poll‐The, B.T.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-2018
• Subjects: Adolescent; Adult; Age; Capacity Profile; Child; Child, Preschool; Clinical trials; Disease Management; disease spectrum; Female; Genetic Association Studies; Genetic disorders; Genotypes; Humans; Male; Mutation; Neurodevelopmental disorders; Patients; peroxisome biogenesis disorder; Phenotype; Phenotypes; phenotypic correlations; Reproducibility of Results; Retrospective Studies; Severity of Illness Index; severity score; Young Adult; Zellweger spectrum disorder; Zellweger Syndrome - diagnosis; Zellweger Syndrome - genetics; severity score; Capacity Profile; Zellweger spectrum disorder; phenotypic correlations; disease spectrum; peroxisome biogenesis disorder
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/cge.13130

The lack of a validated severity scoring system for individuals with Zellweger spectrum disorders (ZSD) hampers optimal patient care and reliable research. Here, we describe the development of such severity score and its validation in a large, well‐characterized cohort of ZSD individuals. We developed a severity scoring system based on the 14 organs that typically can be affected in ZSD. A standardized and validated method was used to classify additional care needs in individuals with neurodevelopmental disabilities (Capacity Profile [CAP]). Thirty ZSD patients of varying ages were scored by the severity score and the CAP. The median score was 9 (range 6‐19) with a median scoring age of 16.0 years (range 2‐36 years). The ZSD severity score was significantly correlated with all 5 domains of the CAP, most significantly with the sensory domain (r = 0.8971, P = <.0001). No correlation was found between age and severity score. Multiple peroxisomal biochemical parameters were significantly correlated with the severity score. The presently reported severity score for ZSD is a suitable tool to assess phenotypic severity in a ZSD patient at any age. This severity score can be used for objective phenotype descriptions, genotype‐phenotype correlation studies, the identification of prognostic features in ZSD patients and for classification and stratification of patients in clinical trials.